The mission of the HIV Prevention Trials Network (HPTN) is to conduct research designed to identify the best combinations of HIV prevention interventions to prevent HIV infection in populations at the highest risk for this infection. The HPTN will be led by Drs. Wafaa EI-Sadr, Columbia University, and Myron S. Cohen, University of North Carolina at Chapel Hill, and supported by experienced operations, laboratory and statistical and data centers. The HPTN will address and support the two research Priority Areas in order to achieve the following eight Specific Aims: Specific Aims for Priority Area 1: Integrate Strategies to Prevent HIV Infection: Aim 1: To develop an integrated strategy to prevent HIV infection in young women in Southern Africa; Aim 2: To develop integrated strategies to prevent HIV infection in men who have sex with men (MSM); Sub-aim 2a: To identify an integrated strategy to prevent HIV acquisition in HIV-uninfected MSM and transgender women in the Americas; Sub-aim 2b: To identify an integrated strategy to prevent HIV transmission from HIV-infected MSM in the United States (U.S.); Aim 3: To develop an integrated strategy to prevent HIV infection in injection drug users (IDUs) in Eastern Europe and Asia; Aim 4: To implement an integrated strategy to virtually eliminate (<1%) HIV transmission in discordant couples in sub-Saharan Africa {SSA}; Aim 5: To develop methods to engage MSM in SSA in prevention research, paving the way for development of an integrated strategy to prevent HIV infection in this population Specific Aims for Priority Area 2: Pre-exposure Prophylaxis {PrEP}: Aim 6: To evaluate the efficacy of an ARV regimen containing maraviroc (MVC) for PrEP; Aim 7: To develop new agents for PrEP with favorable profiles, including long lasting agents; Aim 8: To develop pharmacostatistical models to define the role of new agents for PrEP.